Muscular dystrophy (MD) is a group of muscle diseases that results in increasing weakening

and breakdown of skeletal muscles over time.[1] The disorders differ in which muscles are
primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin.[1]
Many people eventually become unable to walk. Some types are also associated with problems
in other organs.[2]

There are nine main categories of muscular dystrophy that contain more than thirty specific
types.[1][2] The most common type is Duchenne muscular dystrophy (DMD) which typically
affects males beginning around the age of four. Other types include Becker muscular dystrophy,
facioscapulohumeral muscular dystrophy, and myotonic dystrophy.[1] They are due to mutations
in genes that are involved in making muscle proteins. This can occur due to either inheriting the
defect from one's parents or the mutation occurring during early development. Disorders may be
X-linked recessive, autosomal recessive, or autosomal dominant. Diagnosis often involves blood
tests and genetic testing.[2]

There is no cure for muscular dystrophy. Physical therapy, braces, and corrective surgery may
help with some symptoms.[1] Assisted ventilation may be required in those with weakness of
breathing muscles.[2] Medications used include steroids to slow muscle degeneration,
anticonvulsants to control seizures and some muscle activity, and immunosuppressants to delay
damage to dying muscle cells. Outcomes depend on the specific type of disorder.[1]

Duchenne muscular dystrophy, which represents about half of all cases of muscular dystrophy,
affects about one in 5,000 males at birth. Muscular dystrophy was first described in the 1830s by
Charles Bell. The word "dystrophy" is from the Greek dys, meaning "difficult" and troph
meaning "nourish". Gene therapy, as a treatment, is in the early stages of study in humans.[2]

Progressive muscular wasting Calf deformation

Poor balance Limited range of movement

Scoliosis (curvature of the spine and Respiratory difficulty

the back)
Cardiomyopathy
Progressive inability to walk
Muscle spasms
Waddling gait
Gowers' sign
 Dystrophin

These conditions are generally inherited, and the different muscular dystrophies follow
various inheritance patterns. Muscular dystrophy can be inherited by individuals as an X-
linked disorder, a recessive or dominant disorder. Furthermore, it can be a spontaneous
mutation which means errors in the replication of DNA and spontaneous lesions.
Spontaneous lesions are due to natural damage to DNA, where the most common are
depurination and deamination.[4][5]

Dystrophin protein is found in muscle fibre membrane; its helical nature allows it to act
like a spring or shock absorber. Dystrophin links actin in the cytoskeleton and
dystroglycans of the muscle cell plasma membrane, known as the sarcolemma
(extracellular). In addition to mechanical stabilization, dystrophin also regulates calcium
levels.[6][7]

Recent studies on the interaction of proteins with missense mutations and its neighbors
showed high degree of rigidity associated with central hub proteins involved in protein
binding and flexible subnetworks having molecular functions involved with calcium.[8]

Types : Becker muscular dystrophy (BMD) is a less severe variant of Duchenne

muscular dystrophy and is caused by the production of a truncated, but partially
functional form of dystrophin.[9] Survival is usually into old age and affects only boys
(with extremely rare exceptions)[10]

Hydrocephalus

Age at onset is birth, the symptoms include general muscle weakness and possible joint
deformities, disease progresses slowly, and lifespan is shortened. Congenital muscular
dystrophy includes several disorders with a range of symptoms. Muscle degeneration
may be mild or severe. Problems may be restricted to skeletal muscle, or muscle
degeneration may be paired with effects on the brain and other organ systems.[11]

Several forms of the congenital muscular dystrophies are caused by defects in proteins
thought to have some relationship to the dystrophin-glycoprotein complex and to the
connections between muscle cells and their surrounding cellular structure. Some forms of
congenital muscular dystrophy show severe brain malformations, such as lissencephaly
and hydrocephalus.[9]

Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular
dystrophy; it generally affects only boys (with extremely rare exceptions), becoming
clinically evident when a child begins walking. By age 10, the child may need braces for
walking and by age 12, most patients are unable to walk.[12] Lifespans range from 15 to
45, though a few exceptions occur.[12] Researchers have identified the gene for the protein
dystrophin, which when absent, causes DMD.[13] Since the gene is on the X chromosome,
this disorder affects primarily males, and females who are carriers have milder
symptoms. Sporadic mutations in this gene occur frequently.[14]

Dystrophin is part of a complex structure involving several other protein components.

The "dystrophin-glycoprotein complex" helps anchor the structural skeleton
(cytoskeleton) within the muscle cells, through the outer membrane (sarcolemma) of
each cell, to the tissue framework (extracellular matrix) that surrounds each cell. Due to
defects in this assembly, contraction of the muscle leads to disruption of the outer
membrane of the muscle cells and eventual weakening and wasting of the muscle.[9]

Distal muscular dystrophies' age at onset is about 20 to 60 years; symptoms include

weakness and wasting of muscles of the hands, forearms, and lower legs; progress is
slow and not life-threatening.[15]

Miyoshi myopathy, one of the distal muscular dystrophies, causes initial weakness in the
calf muscles, and is caused by defects in the same gene responsible for one form of limb-
 girdle muscular dystrophy.[9]

EmeryDreifuss muscular dystrophy patients normally present in childhood and the early
teenaged years with contractures. Clinical signs include muscle weakness and wasting,
starting in the distal limb muscles and progressing to involve the limb-girdle muscles.
Most patients also suffer from cardiac conduction defects and arrhythmias.[16][17]

The three subtypes of EmeryDreifuss MD are distinguishable by their pattern of

inheritance: X-linked, autosomal dominant, and autosomal recessive. The X-linked form
is the most common. Each type varies in prevalence and symptoms. The disease is
caused by mutations in the LMNA gene, or more commonly, the EMD gene. Both genes
encode for protein components of the nuclear envelope. However, how these mutations
cause the pathogenesis is not well understood.[18]

Timelapse expression of DUX4 protein in FSHD cells

Facioscapulohumeral muscular dystrophy (FSHD) initially affects the muscles of the

face, shoulders, and upper arms with progressive weakness.[19]

Symptoms usually develop in early adulthood (late teens); affected individuals become
severely disabled. The pattern of inheritance is autosomal dominant, though a number of
spontaneous mutations occur. Two defects are needed for FSHD, which for the first time
provides a unifying theory for the underlying genetics of FSHD.[9][20]

FSHD occurs both in males and females.[21]

Limb-girdle muscular dystrophy (LGMD) affects both boys and girls.[22] LGMDs all show
a similar distribution of muscle weakness, affecting both upper arms and legs. Many
forms of LGMD have been identified, showing different patterns of inheritance
(autosomal recessive vs. autosomal dominant). In an autosomal recessive pattern of
inheritance, an individual receives two copies of the defective gene, one from each
parent. The recessive LGMDs are more frequent than the dominant forms, and usually
have childhood or teenaged onset. The dominant LGMDs usually show adult onset.
Some of the recessive forms have been associated with defects in proteins that make up
the dystrophin-glycoprotein complex.[9] Though a person normally leads a normal life
with some assistance, in some extreme cases, death from LGMD occurs due to
cardiopulmonary complications.[23]
Myotonic muscular dystrophy is an autosomal dominant condition that presents with
myotonia (delayed relaxation of muscles), as well as muscle wasting and weakness.[24]
Myotonic MD varies in severity and manifestations and affects many body systems in
addition to skeletal muscles, including the heart, endocrine organs, and eyes.[25]

Myotonic MD type 1 (DM1) is the most common adult form of muscular dystrophy. It
results from the expansion of a short (CTG) repeat in the DNA sequence of the myotonic
dystrophy protein kinase gene. Myotonic muscular dystrophy type 2 (DM2) is rarer and
is a result of the expansion of the CCTG repeat in the zinc finger protein 9 gene.[9]

Oculopharyngeal MD's age at onset is 40 to 70 years; symptoms affect muscles of

eyelids, face, and throat followed by pelvic and shoulder muscle weakness; it has been
attributed to a short repeat expansion in the genome which regulates the translation of
some genes into functional proteins.[9]

Diagnosis : The diagnosis of muscular dystrophy is based on the results of muscle

biopsy, increased creatine phosphokinase (CpK3), electromyography, and genetic testing.
A physical examination and the patient's medical history will help the doctor determine
the type of muscular dystrophy. Specific muscle groups are affected by different types of
muscular dystrophy.[26] Other tests that can be done are chest X-ray, echocardiogram, CT
 scan, and magnetic resonance image scan, which via a magnetic field can produce images
whose detail helps diagnose muscular dystrophy.[27]

Management : Ankle foot orthosis

Currently, there is no cure for muscular dystrophy. In terms of management, physical
therapy, occupational therapy, orthotic intervention (e.g., ankle-foot orthosis),[28][29] speech
therapy, and respiratory therapy may be helpful.[28] Low intensity corticosteroids such as
prednisone, and deflazacort may help to maintain muscle tone.[30] Orthoses (orthopedic
appliances used for support) and corrective orthopedic surgery may be needed to improve
the quality of life in some cases.[2] The cardiac problems that occur with EDMD and
myotonic muscular dystrophy may require a pacemaker.[31] The myotonia (delayed
relaxation of a muscle after a strong contraction) occurring in myotonic muscular
dystrophy may be treated with medications such as quinine.[32] Occupational therapy
assists the individual with MD to engage in activities of daily living (such as self-feeding
and self-care activities) and leisure activities at the most independent level possible. This
may be achieved with use of adaptive equipment or the use of energy-conservation
techniques. Occupational therapy may implement changes to a person's environment,
both at home or work, to increase the individual's function and accessibility; furthermore,
it addresses psychosocial changes and cognitive decline which may accompany MD, and
provides support and education about the disease to the family and individual.

Prognosis : Prognosis depends on the individual form of MD. In some cases, a

[33]

person with a muscle disease will get progressively weaker to the extent that it shortens
lifespan due to heart and breathing complications. However, some of the muscle diseases
do not affect life expectancy at all, and ongoing research is attempting to find cures and
treatments to slow muscle weakness.[2]

Historyedi : In the 1860s, descriptions of boys who grew progressively weaker,

lost the ability to walk, and died at an early age became more prominent in medical
journals. In the following decade,[34] French neurologist Guillaume Duchenne gave a
comprehensive account of the most common and severe form of the disease, which now
carries his nameDuchenne MD. It soon became evident that the disease had more than
one form.[35] The other major forms are Becker, limb-girdle, congenital,
facioscapulohumeral, myotonic, oculopharyngeal, distal, and EDMD.[9] Duchenne and
Becker muscular dystrophies, being caused by a mutation of a gene located on the X
chromosome, predominantly affect males, although females can sometimes have severe
symptoms, as well. Most types of MD are multisystem disorders with manifestations in
body systems including the heart, gastrointestinal system, nervous system, endocrine
glands, eyes, and brain.[9]